Respiratory System Commons^™

Targeting Transitioning Lung Monocytes/Macrophages As Treatment Strategies In Lung Disease Related To Environmental Exposures, Aaron Schwab, Todd A. Wyatt, Grace Moravec, Geoffrey M. Thiele, Amy J. Nelson, Angela Gleason, Oliver Schanze, Michael J. Duryee, Debra J. Romberger, Ted R. Mikuls, Jill A. Poole

Journal Articles: Pulmonary & Critical Care Med

Background: Environmental/occupational exposures cause significant lung diseases. Agricultural organic dust extracts (ODE) and bacterial component lipopolysaccharide (LPS) induce recruited,transitioning murine lung monocytes/macrophages, yet their cellular role remains unclear.

Methods: CCR2 RFP⁺ mice were intratracheally instilled with high concentration ODE (25%), LPS (10 μg), or gram-positive peptidoglycan (PGN, 100 μg) for monocyte/macrophage cell-trafficking studies. CCR2 knockout (KO) mice and administration of intravenous clodronate liposomes strategies were employed to reduce circulating monocytes available for lung recruitment following LPS exposure.Lung tissues and bronchoalveolar lavage fluid (BALF) were collected. Pro-inflammatory and/or pro-fibrotic cytokines, chemokines, and lung extracellular matrix mediators were quantitated by ELISA. …

Lung-Delivered Il-10 Therapy Elicits Beneficial Effects Via Immune Modulation In Organic Dust Exposure-Induced Lung Inflammation, Aaron D. Schwab, Todd A. Wyatt, Amy J. Nelson, Angela Gleason, Rohit Gaurav, Debra J. Romberger, Jill A. Poole

Journal Articles: Pulmonary & Critical Care Med

Efficacious therapeutic options capable of resolving inflammatory lung disease associated with environmental and occupational exposures are lacking. This study sought to determine the preclinical therapeutic potential of lung-delivered recombinant interleukin (IL)-10 therapy following acute organic dust exposure in mice. Here, C57BL/6J mice were intratracheally instilled with swine confinement organic dust extract (ODE) (12.5%, 25%, 50% concentrations) with IL-10 (1 μg) treatment or vehicle control intratracheally-administered three times: 5 hr post-exposure and then daily for 2 days. The results showed that IL-10 treatment reduced ODE (25%)-induced weight loss by 66% and 46% at Day 1 and Day 2 post-exposure, respectively. IL-10 …

Loss Of Cftr Function In Macrophages Alters The Cell Transcriptional Program And Delays Lung Resolution Of Inflammation, Dianne Wellems, Yawen Hu, Scott Jennings, Guoshun Wang

School of Graduate Studies Faculty Publications

Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CF Transmembrane-conductance Regulator (CFTR) gene. The most severe pathologies of CF occur in the lung, manifesting as chronic bacterial infection, persistent neutrophilic inflammation, and mucopurulent airway obstruction. Despite increasing knowledge of the CF primary defect and the resulting clinical sequelae, the relationship between the CFTR loss of function and the neutrophilic inflammation remains incompletely understood. Here, we report that loss of CFTR function in macrophages causes extended lung inflammation. After intratracheal inoculation with Pseudomonas aeruginosa, mice with a macrophage-specific Cftr-knockout (Mac-CF) were able to mount an …

Agricultural Dust Derived Bacterial Extracellular Vesicle Mediated Inflammation Is Attenuated By Dha, Art J. Heires, Derrick R. Samuelson, Daniel Villageliu, Tara M. Nordgren, Debra J. Romberger

Journal Articles: Pulmonary & Critical Care Med

Dietary long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and their pro-resolving metabolites are protective against atherosclerotic disease, and ameliorate systemic inflammatory conditions including lupus erythematosus, psoriasis, and bronchial asthma. Organic bioaerosol inhalation is a common and injurious hazard associated with agricultural occupations such as work in swine concentrated animal feeding operations (CAFOs) and is known to increase the risk for developing respiratory conditions such as asthma and COPD. Nearly all cells secrete membrane-bound vesicles (extracellular vesicles, EVs) that have the capacity to transmit protein, nucleic acid, and lipid signaling mediators between cells. Using a polymer-based isolation technique (ExoQuick, PEG) followed …

Outcomes Of Covid-19 Infection In Patients With Hematological Malignancies- A Multicenter Analysis From Pakistan, Adeeba Zaki, Salman Muhammad Soomar, Danish Hasan Khan, Hasan Shaharyar Sheikh, Raheel Iftikhar, Ayaz Mir, Zeba Aziz, Khadija Bano, Hafsa Naseer, Qamar Un-Nisa Chaudhry

Section of Haematology/Oncology

Purpose: COVID-19 infection resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began to spread across the globe in early 2020. Patients with hematologic malignancies are supposed to have an increased risk of mortality from coronavirus disease of 2019 (COVID-19) infection. From Pakistan, we report the analysis of the outcome and interaction between patient demographics and tumor subtype and COVID-19 infection and hematological malignancy.
Patients and methods: This multicenter, retrospective study included adult patients with a history of histologically proven hematological malignancies who were tested positive for COVID-19 via PCR presented at the oncology department of 5 tertiary care hospitals …

The Who Global Tuberculosis 2021 Report - Not So Good News And Turning The Tide Back To End Tb, Chakaya Jeremiah, Eskild Petersen, Rebecca Nantanda, Brenda N. Mungai, Giovanni Battista Migliori, Farhana Amanullah, Patrick Lungu, Francine Ntoumi, Nagalingeswaran Kumarasamy

Department of Paediatrics and Child Health

Objective: To review the data presented in the 2021 WHO global TB report and discuss the current constraints in the global response.
Introduction and methods: The WHO global TB reports, consolidate TB data from countries and provide up to date assessment of the global TB epidemic. We reviewed the data presented in the 2021 report.
Results: We noted that the 2021 WHO global TB report presents a rather grim picture on the trajectory of the global epidemic of TB including a stagnation in the annual decline in TB incidence, a decline in TB notifications and an increase in estimated TB …

Pulmonary Adenoid Cystic Carcinoma Presenting Late With Intrapericardial Extension: Case Report, Manzar Abbas, Usama Qamar, Syeda Maria Ahmad Zaidi, Faiqa Binte Aamir, Ali Aahil Noorali, Haseeb Ur Rahman, Saulat Hasnain Fatimi

Medical College Documents

Adenoid cystic carcinoma, also known as cylindroma, is one of the rare and unexplored clinical presentations of lung cancer, for which existing knowledge is scarce. This case report discusses a presentation of this tumor in the right lung, which subsequently extended to the left atrium through the right superior pulmonary vein. The extension of this rare tumor into the left atrium makes this case both uniquely distinctive and clinically relevant. The management strategy opted for this case was a right posterolateral thoracotomy and right pneumonectomy with partial resection of the left atrium. The desired outcome of this report is to …

Risk Factors For Acute Respiratory Infections In Children Between 0 And 23 Months Of Age In A Peri-Urban District In Pakistan: A Matched Case–Control Study, Fatima Mir, Shabina Ariff, Maria Asif Bhura, Suhail Chanar, Aspara Ali, Muhammad Jawwad, A Hussain, Arjumand Rizvi, Muhammad Umer, Zahid Memon, Atif Habib, Sajid Bashir Soofi, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Background: Acute respiratory infection (ARI) accounts for nearly 15% of all childhood mortality in South Asia, with children from rural areas at higher risk due to inaccessibility to healthcare facilities. We therefore aimed to identify risk factors associated with ARI in children under 2 years of age in rural Pakistan.
Methods: A retrospective 1:2 matched case-control study was conducted between October and December 2018 in Taluka Kotri, Jamshoro District of Pakistan. Cases were identified as children between 0 and 23 months of age with a history of fever, cough, sore throat, fast breathing, difficulty breathing, or chest indrawing in the …

Relationships Of Serum Cc16 Levels With Smoking Status And Lung Function In Copd, Kelli C. Gribben, Jill A. Poole, Amy J. Nelson, Paraskevi A. Farazi, Christopher S. Wichman, Art J. Heires, Debra J. Romberger, Tricia D. Levan

Journal Articles: Pulmonary & Critical Care Med

Background: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown.

Methods: Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV₁/FVC ratio < 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation.

Results: The study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on …

Optimizing Antidotal Treatment With The Oral Hsp90 Inhibitor Tas-116 Against Hydrochloric Acid-Induced Pulmonary Fibrosis In Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropolou, Tierney Day, John Catravas

Bioelectrics Publications

Exposure to high concentrations of hydrochloric acid (HCl) can lead to severe acute and chronic lung injury. In the aftermath of accidental spills, victims may be treated for the acute symptoms, but the chronic injury is often overlooked. We have developed a mouse model of acute and chronic lung injury, in which the peak of acute lung injury occurs on the day 4 after HCl exposure. We have also demonstrated that HSP90 inhibitors are effective antidotes when administered starting 24 h after HCl. In this study we examined the hypothesis that the novel oral HSP90 inhibitor TAS-116 can effectively ameliorate …

Assessment Of Combined Modality Therapy For Non-Small-Cell Lung Carcinoma: A Simulation Study Concerning Concurrent Chemo-Brachytherapy, Hadi Rezaei, Hesameddin Mostaghimi, Ali Reza Mehdizadeh

Electrical & Computer Engineering Faculty Publications

Although surgery is the treatment of choice for early-stage non-small-cell lung carcinoma, almost two-thirds of patients do not have acceptable pulmonary function for extensive surgeries. The alternative approach for this large group of patients is sublobar resection along with low-dose-rate (LDR) brachytherapy (BT). However, patients with resected lungs have a high risk of recurrence and are often treated with platinum-based (Pt-based) chemotherapy (CT). In this study, we aimed to evaluate the absorbed doses of lung and other thoracic organs, considering concurrent chemo-BT with LDR sources in two modalities: conventional vs. unconventional Pt-based CT. We used the MCNPX code for simulations …

Sex-Related Differences In Murine Models Of Chemically Induced Pulmonary Fibrosis, Pavel Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

We developed two models of chemically induced chronic lung injury and pulmonary fibrosis in mice (intratracheally administered hydrochloric acid (HCl) and intratracheally administered nitrogen mustard (NM)) and investigated male-female differences. Female mice exhibited higher 30-day survival and less weight loss than male mice. Thirty days after the instillation of either HCl or NM, bronchoalveolar lavage fluid displayed a persistent, mild inflammatory response, but with higher white blood cell numbers and total protein content in males vs. females. Furthermore, females exhibited less collagen deposition, milder pulmonary fibrosis, and lower Ashcroft scores. After instillation of either HCl or NM, all animals displayed …

Efficacy Of Pulmonary Ultrasound Compared To N-Terminal Prohormone Brain Natriuretic Peptide As A Diagnostic Tool For Congestive Heart Failure In Patients Presenting With Acute Dyspnea In The Emergency Setting, Leah Krohn, Michael Burns

Physician Assistant Capstones, 2020-current

Objective: To determine the efficacy of using pulmonary ultrasound as a diagnostic tool in acute dyspnea of undetermined cause compared to the use of serum N-Terminal prohormone Brain Natriuretic Peptide (NT-proBNP) in the diagnosis of heart failure.

Design: Systematic literature review

Methods: Searches were conducted in PubMed and Scopus using the terms pulmonary ultrasound and congestive heart failure and studies within the last 10 years. Studies that used pulmonary ultrasound compared to BNP as a marker for the diagnosis of heart failure were included.

Results: All three studies found that the use of pulmonary ultrasound was a more specific …

Age Based Evaluation Of Nut Aspiration Risk., Jill N D'Souza, Taher S Valika, Bharat Bhushan, Jonathan B Ida

School of Medicine Faculty Publications

Objective: To identify an age at which initiation of whole nut into the pediatric diet could be considered safe, by evaluating the age distribution of children undergoing bronchoscopy with removal of nut or seed material from the airway. Method: A retrospective chart review over a ten-year period identifying children age 0–18 that have undergone bronchoscopy with retrieval of airway foreign bodies. A statistical analysis of demographic data was carried out to identify age distribution of aspiration events. Results: Sixty-four cases of foreign body aspiration were identified, of which 43 (67%) were of organic origin, specifically nuts. A Fisher's exact test …

Exogenous Lipoid Pneumonia Complicated By Mineral Oil Asperation In A Patient With Chronic Constipation: A Case Report And Review, Hafiz Muhammad Jeelani, Muhammad Mubbashir Sheikh, Belaal Sheikh, Hafiz Mahboob, Anchit Bharat

School of Medicine Faculty Publications

Exogenous lipoid pneumonia is a rare and frequently misdiagnosed lung disease. It occurs as an inflammatory reaction secondary to either aspiration or inhalation of lipids. Our patient had a history significant for recurrent pneumonia and the use of mineral oil for chronic constipation. A chest computed tomography showed multifocal consolidative opacities with areas of low attenuation, highly suspicious of exogenous lipid pneumonia. The diagnosis was confirmed with combined bronchoalveolar lavage and transbronchial lung biopsy that showed lipid-laden macrophages consistent with exogenous lipoid pneumonia. After thorough medication review, apart from mineral oil, no other contributing factors were found. A diagnosis of …

Syllabus For Clinical Exercise Physiology (Kine 4700), Phillip Drouet

Q2S Enhancing Pedagogy

The syllabus has newly developed learning objectives that will prepare students entering the field of clinical exercise physiology. This course will cover the etiology and pathophysiology of many chronic diseases that plague the population. Assessments of chronic diseases include but are not limited to understanding symptomology will also be covered. Due to the limitations in time the most prevalent chronic disease will be covered and students will have to present on a disease that was not presented in class. The practical application portion of this course will take place during a lab section. Here students will have the opportunity to …

Budesonide Enhances Agonist-Induced Bronchodilation In Human Small Airways By Increasing Camp Production In Airway Smooth Muscle, Cynthia J. Koziol-White, Timothy B. Johnstone, Maia L. Corpuz, Gaoyuan Cao, Sarah Orfanos, Vishal Parikh, Brian Deeney, Omar Tliba, Rennolds S. Ostrom, Ian Dainty, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

The non-genomic mechanisms by which glucocorticoids modulate β₂ agonist-induced-bronchodilation remain elusive. Our studies aimed to elucidate mechanisms mediating the beneficial effects of glucocorticoids on agonist-induced bronchodilation. Utilizing human precision cut lung slices (hPCLS), we measured bronchodilation to formoterol, prostaglandin E₂ (PGE₂), cholera toxin (CTX) or forskolin in the presence and absence of budesonide. Using cultured human airway smooth muscle (HASM), intracellular cAMP was measured in live cells following exposure to formoterol, PGE₂, or forskolin in the presence or absence of budesonide. We showed that simultaneous budesonide administration amplified formoterol-induced bronchodilation and attenuated agonist-induced phosphorylation …

Transforming Growth Factor-Β1 Decreases Β2-Agonist–Induced Relaxation In Human Airway Smooth Muscle, Christie A. Ojiaku, Elena Chung, Vishal Parikh, Jazmean K. Williams, Anthony Schwab, Ana Lucia Fuentes, Maia L. Corpuz, Victoria Lui, Sam Paek, Natalia M. Bexiga, Shreya Narayan, Francisco J. Nunez, Kwangmi An, Rennolds S. Ostrom, Steven S. An, Reynold A. Pannettieri Jr.

Pharmacy Faculty Articles and Research

Helper T effector cytokines implicated in asthma modulate the contractility of human airway smooth muscle (HASM) cells. We have reported recently that a profibrotic cytokine, transforming growth factor (TGF)-β1, induces HASM cell shortening and airway hyperresponsiveness. Here, we assessed whether TGF-β1 affects the ability of HASM cells to relax in response to β₂-agonists, a mainstay treatment for airway hyperresponsiveness in asthma. Overnight TGF-β1 treatment significantly impaired isoproterenol (ISO)-induced relaxation of carbachol-stimulated, isolated HASM cells. This single-cell mechanical hyporesponsiveness to ISO was corroborated by sustained increases in myosin light chain phosphorylation. In TGF-β1–treated HASM cells, ISO evoked markedly lower …

Patients' Perceptions And Patient-Reported Outcomes In Progressive-Fibrosing Interstitial Lung Diseases, Jeffrey J. Swigris, Kevin K. Brown, Rayid Abdulqawi, Ketan Buch, Daniel F. Dilling, Dirk Koschel, Krishna Thavarajah, Rade Tomic, Yoshikazu Inoue

Internal Medicine Faculty Publications

The effects of interstitial lung disease (ILD) create a significant burden on patients, unsettling almost every domain of their lives, disrupting their physical and emotional well-being and impairing their quality of life (QoL). Because many ILDs are incurable, and there are limited reliably-effective, life-prolonging treatment options available, the focus of many therapeutic interventions has been on improving or maintaining how patients with ILD feel and function, and by extension, their QoL. Such patient-centred outcomes are best assessed by patients themselves through tools that capture their perceptions, which inherently incorporate their values and judgements. These patient-reported outcome measures (PROs) can be …

A Multicenter Study To Evaluate Pulmonary Function In Osteogenesis Imperfecta., Allison Tam, Shan Chen, Evan Schauer, Ingo Grafe, Venkata Bandi, Jay R. Shapiro, Robert D. Steiner, Peter A. Smith, Michael B. Bober, Tracy Hart, David Cuthbertson, Jeffrey Krischer, Mary Mullins, Peter H. Byers, Robert A. Sandhaus, Michaela Durigova, Francis H. Glorieux, Frank Rauch, Vernon Reid Sutton, Brendan Lee, Members Of The Brittle Bone Disorders Consortium, Eric T. Rush, Sandesh C S Nagamani

Manuscripts, Articles, Book Chapters and Other Papers

Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that have systematically evaluated pulmonary function in individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) and forced expiratory volume in the first second (FEV₁ ), in a large cohort of individuals with OI (n = 217) enrolled in a multicenter, observational study. We show that individuals with the more severe form of the disease, OI type III, have significantly reduced FVC and FEV₁ which do not follow the expected trends of the …

Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel

Pharmaceutical Sciences Faculty Publications

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized …

The South Sudan: Tuberculosis, Blake Schwarz

Global Public Health

The South Sudan is a country that recently gained independence from the Sudan after a bloody twenty year civil war. They lost nearly two million lives during the war, and are now ravaged by Tuberculosis, or TB. After gaining their independence in 2011, the South Sudan has an average of 18,000 cases of TB at any time. This would consider TB in the South Sudan an endemic, as it always has a base level of TB cases that does not vary. There is medication for TB that is available to the citizens on the South Sudan, but the prescription is …

Hypersensitivity Of Vagal Pulmonary Afferents Induced By Tumor Necrosis Factor Alpha In Mice, Ruei-Lung Lin, Qihai Gu, Lu-Yuan Lee

Physiology Faculty Publications

Tumor necrosis factor alpha (TNFα), a pro-inflammatory cytokine, plays a significant role in the pathogenesis of allergic asthma. Inhalation of TNFα also induces airway hyperresponsiveness in healthy human subjects, and the underlying mechanism is not fully understood. A recent study reported that TNFα caused airway inflammation and a sustained elevation of pulmonary chemoreflex responses in mice, suggesting a possible involvement of heightened sensitivity of vagal pulmonary C-fibers. To investigate this possibility, the present study aimed to investigate the effect of a pretreatment with TNFα on the sensitivity of vagal pulmonary afferents in anesthetized mice. After TNFα (10 μg/ml, 0.03 ml) …

Cigarette Smoke Impairs A2a Adenosine Receptor Mediated Wound Repair Through Up-Regulation Of Duox-1 Expression., Zhi Tian, Hui Zhang, Jendayi Dixon, Nicole Traphagen, Todd A. Wyatt, Kusum K. Kharbanda, Samantha Simet, Narasaiah Kolliputi, Diane S Allen-Gipson

Journal Articles: Pulmonary & Critical Care Med

Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice. Cells were treated with 5% CS extract (CSE) for various periods of time, and mice were exposed to whole body CS for six weeks. Both CSE and …

Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Organic hog barn dust (HDE) exposure induces lung inflammation and long-term decreases in lung function in agricultural workers. While concentrations of common gasses in confined animal facilities are well characterized, few studies have been done addressing if exposure to elevated barn gasses impacts the lung immune response to organic dusts. Given the well documented effects of hypercapnia at much higher levels we hypothesized that CO2 at 8 h exposure limit levels (5000 ppm) could alter innate immune responses to HDE.

METHODS: Using a mouse model, C57BL/6 mice were nasally instilled with defined barn dust extracts and then housed in …

Effect Of Low-Level Co2 On Innate Inflammatory Protein Response To Organic Dust From Swine Confinement Barns., David Schneberger, Jane M. Devasure, Kristina L. Bailey, Debra J. Romberger, Todd A. Wyatt

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Organic hog barn dust (HDE) exposure induces lung inflammation and long-term decreases in lung function in agricultural workers. While concentrations of common gasses in confined animal facilities are well characterized, few studies have been done addressing if exposure to elevated barn gasses impacts the lung immune response to organic dusts. Given the well documented effects of hypercapnia at much higher levels we hypothesized that CO2 at 8 h exposure limit levels (5000 ppm) could alter innate immune responses to HDE.

METHODS: Using a mouse model, C57BL/6 mice were nasally instilled with defined barn dust extracts and then housed in …

Early Cumulative Supplemental Oxygen Predicts Bronchopulmonary Dysplasia In High Risk Extremely Low Gestational Age Newborns., Katherine C. Wai, Michael A. Kohn, Roberta A. Ballard, William E. Truog, Dennis M. Black, Jeanette M. Asselin, Philip L. Ballard, Elizabeth E. Rogers, Roberta L. Keller, Trial Of Late Surfactant (Tolsurf) Study Group

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To assess the prognostic accuracy of early cumulative supplemental oxygen (CSO) exposure for prediction of bronchopulmonary dysplasia (BPD) or death, and to evaluate the independent association of CSO with BPD or death.

STUDY DESIGN: We performed a secondary analysis of the Trial of Late Surfactant, which enrolled 511 infants born at ≤28 weeks gestational age who were mechanically ventilated at 7-14 days of life. Our primary outcome was BPD or death at 36 weeks postmenstrual age, as determined by a physiological oxygen/flow challenge. Average daily supplemental oxygen (fraction of inspired oxygen - 0.21) was calculated. CSO was calculated as …

Hdac6 Inhibition Prevents Tnf-Α-Induced Caspase 3 Activation In Lung Endothelial Cell And Maintains Cell-Cell Junctions, Jinyan Yu, Mengshi Ma, Zhongsen Ma, Jian Fu

Center for Research on Environmental Disease Faculty Publications

Pro-inflammatory mediators such as TNF-α induce caspase activation in endothelial cells, which leads to degradation of cellular proteins, induction of apoptotic signaling, and endothelial cell dysfunction. New therapeutic agents that can inhibit caspase activation may provide protection against inflammatory injury to endothelial cells. In the present study, we examined the effects of selective histone deacetylase 6 (HDAC6) inhibition on TNF-α induced caspase 3 activation and cell-cell junction dysfunction in lung endothelial cells. We also assessed the protective effects of HDAC6 inhibition against lung inflammatory injury in a mouse model of endotoxemia. We demonstrated that selective HDAC6 inhibition or knockdown of …

Myd88 In Lung Resident Cells Governs Airway Inflammatory And Pulmonary Function Responses To Organic Dust Treatment., Jill A. Poole, Todd A. Wyatt, Debra J. Romberger, Elizabeth Staab, Samantha Simet, Stephen J. Reynolds, Joseph H. Sisson, Tammy Kielian

Journal Articles: Pulmonary & Critical Care Med

Inhalation of organic dusts within agriculture environments contributes to the development and/or severity of airway diseases, including asthma and chronic bronchitis. MyD88 KO (knockout) mice are nearly completely protected against the inflammatory and bronchoconstriction effects induced by acute organic dust extract (ODE) treatments. However, the contribution of MyD88 in lung epithelial cell responses remains unclear. In the present study, we first addressed whether ODE-induced changes in epithelial cell responses were MyD88-dependent by quantitating ciliary beat frequency and cell migration following wounding by electric cell-substrate impedance sensing. We demonstrate that the normative ciliary beat slowing response to ODE is delayed in …

Cfap54 Is Required For Proper Ciliary Motility And Assembly Of The Central Pair Apparatus In Mice., Casey W. Mckenzie, Branch Craige, Tiffany V. Kroeger, Rozzy Finn, Todd A. Wyatt, Joseph H. Sisson, Jacqueline A. Pavlik, University Of Massachusetts Medical School, Gregory M. Hendricks, George B. Witman, Lance Lee

Journal Articles: Pulmonary & Critical Care Med

Motile cilia and flagella play critical roles in fluid clearance and cell motility, and dysfunction commonly results in the pediatric syndrome primary ciliary dyskinesia (PCD). CFAP221, also known as PCDP1, is required for ciliary and flagellar function in mice and Chlamydomonas reinhardtii, where it localizes to the C1d projection of the central microtubule apparatus and functions in a complex that regulates flagellar motility in a calcium-dependent manner. We demonstrate that the genes encoding the mouse homologues of the other C. reinhardtii C1d complex members are primarily expressed in motile ciliated tissues, suggesting a conserved function in mammalian motile cilia. The …